The G protein coupled pathway, the best understood of all signaling networks, has a large number of molecular elements that interact with each other either simultaneously or in a particular order at well-mapped surface areas of the proteins. This pathway is important to human health evident by the fact that over half the drugs on the market today target this pathway. Given great progress in genome sequencing and structure solutions, we are at a juncture when sufficient knowledge on G protein signaling is available in diverse organisms such that we can solve how this pathway evolved from its primordial form to the complexities seen today in humans. This is the first opportunity to determine how complexity in signaling is built and how evolution of the individual components of the signaling network constrain the evolution of other or all components. Upon completion of our goals, we will have inventoried, using an informative set of organisms, the G protein repertoire and deduced the lineage of these components and how changes in the repertoire came about. We will have determine at the molecular level the changes that occurred to bring about new functionality of the core components of this signaling pathway over time and shown that these changes caused changes in functionality. We will have shown how molecular interactions drive and block evolution. We will have shown the range of functionalities that can be accomplished with several unique G protein repertoires, opening up new possibilities for engineering the G protein pathway to alleviate disease or to improve agriculture.
This application requests internal funds be allocated for a meeting to bring together a small group of critical and very diverse experts to determine how to solve this problem, to agree on a division of labor, and to devise a strategy to obtain external funding to enable us to reach the stated goals.